The proposed studies are a continuation of previous investigations on the inhomogeneity of human and animal hemoglobin types. 1. A study of human hemoglobin variants will be made by precise chemical and functional analyses. Newly developed methods, including high performance liquid chromatography (HPLC) will be applied. Results from these studies will give insight into the nature of disease states and the functional and physico-chemical properties of normal and abnormal hemoglobins. 2. The chemical analyses of human fetal hemoglobins present in normal and pathological conditions will continue. Data from these analyses will further define the Hb F heterogeneity in the various forms of thalassemia, the HPFH conditions, other hemoglobinopathies, and acquired hematological disorders. 3. Newly developed methods using HPLC have refined methodology to quantitate the types of gamma chains, and presently available procedures will make it possible to study the synthesis of G gamma and A gamma chains in CFU-E and BFU-E derived colonies from bone marrow and peripheral blood samples of patients with numerous abnormal hematological conditions, normal adults and newborn. These studies will help define normal mechanisms of protein synthesis and the malfunction of some of these mechanisms in disease states. The ultimate goal will be to find means to effectively influence some of these mechanisms, mainly the activation/deactivation of structural genes. 4. Sequential analyses of alpha and Beta chains of deer hemoglobins will continue and hopefully will provide data useful for the understanding of the mechanisms of Hb aggregation in this animal species and, indirectly, in patients with sickle cell anemia.